An atlas connecting shared genetic architecture of human diseases and molecular phenotypes provides insight into COVID-19 susceptibility

被引：38

作者：

Wang, Liuyang ^{[1
]}

Balmat, Thomas J. ^{[2
]}

Antonia, Alejandro L. ^{[1
]}

Constantine, Florica J. ^{[3
]}

Henao, Ricardo ^{[3
]}

Burke, Thomas W. ^{[3
]}

Ingham, Andy ^{[2
]}

McClain, Micah T. ^{[3
,4
,5
]}

Tsalik, Ephraim L. ^{[1
,3
,4
,5
]}

Ko, Emily R. ^{[3
,6
]}

Ginsburg, Geoffrey S. ^{[3
]}

DeLong, Mark R. ^{[2
]}

Shen, Xiling ^{[7
]}

Woods, Christopher W. ^{[3
,4
,5
]}

Hauser, Elizabeth R. ^{[8
,9
,10
]}

Ko, Dennis C. ^{[1
,5
]}

机构：

[1] Duke Univ, Dept Mol Genet & Microbiol, Sch Med, 0049 CARL Bldg Box 3053,213 Res Dr, Durham, NC 27710 USA

[2] Duke Univ, Duke Res Comp, Durham, NC 27710 USA

[3] Duke Univ, Ctr Appl Genom & Precis Med, Dept Med, Durham, NC 27710 USA

[4] Durham Vet Affairs Hlth Care Syst, Durham, NC 27705 USA

[5] Duke Univ, Div Infect Dis, Dept Med, Med Ctr, Durham, NC 27710 USA

[6] Duke Reg Hosp, Dept Hosp Med, Durham, NC 27705 USA

[7] Duke Univ, Dept Biomed Engn, Woo Ctr Big Data & Precis Hlth, Durham, NC 27710 USA

[8] Duke Univ, Duke Mol Physiol Inst, Med Ctr, Durham, NC 27710 USA

[9] Duke Univ, Dept Biostat & Bioinformat, Med Ctr, Durham, NC 27710 USA

[10] Durham VA Hlth Care Syst, Cooperat Studies Program Epidemiol Ctr Durham, Durham, NC 27705 USA

来源：

GENOME MEDICINE | 2021年 / 13卷 / 01期

关键词：

Pleiotropy; Cross-phenotype association; Gout; LD-score; Colocalization; PheWAS; Hi-HOST; Idiopathic pulmonary fibrosis; Macular telangiectasia; rs2869462; rs505922; rs12610495; GENOME-WIDE ASSOCIATION; VON-WILLEBRAND-FACTOR; ABO BLOOD-GROUP; AFRICAN-AMERICANS; KIDNEY-STONES; RISK LOCI; GROUP-B; GROUP-A; GOUT; VARIANTS;

D O I：

10.1186/s13073-021-00904-z

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background While genome-wide associations studies (GWAS) have successfully elucidated the genetic architecture of complex human traits and diseases, understanding mechanisms that lead from genetic variation to pathophysiology remains an important challenge. Methods are needed to systematically bridge this crucial gap to facilitate experimental testing of hypotheses and translation to clinical utility. Results Here, we leveraged cross-phenotype associations to identify traits with shared genetic architecture, using linkage disequilibrium (LD) information to accurately capture shared SNPs by proxy, and calculate significance of enrichment. This shared genetic architecture was examined across differing biological scales through incorporating data from catalogs of clinical, cellular, and molecular GWAS. We have created an interactive web database (interactive Cross-Phenotype Analysis of GWAS database (iCPAGdb)) to facilitate exploration and allow rapid analysis of user-uploaded GWAS summary statistics. This database revealed well-known relationships among phenotypes, as well as the generation of novel hypotheses to explain the pathophysiology of common diseases. Application of iCPAGdb to a recent GWAS of severe COVID-19 demonstrated unexpected overlap of GWAS signals between COVID-19 and human diseases, including with idiopathic pulmonary fibrosis driven by the DPP9 locus. Transcriptomics from peripheral blood of COVID-19 patients demonstrated that DPP9 was induced in SARS-CoV-2 compared to healthy controls or those with bacterial infection. Further investigation of cross-phenotype SNPs associated with both severe COVID-19 and other human traits demonstrated colocalization of the GWAS signal at the ABO locus with plasma protein levels of a reported receptor of SARS-CoV-2, CD209 (DC-SIGN). This finding points to a possible mechanism whereby glycosylation of CD209 by ABO may regulate COVID-19 disease severity. Conclusions Thus, connecting genetically related traits across phenotypic scales links human diseases to molecular and cellular measurements that can reveal mechanisms and lead to novel biomarkers and therapeutic approaches. The iCPAGdb web portal is accessible at and the software code at .

引用

页数：19

共 118 条

[1] Genome-wide Association Study Identifies 27 Loci Influencing Concentrations of Circulating Cytokines and Growth Factors [J].

Ahola-Olli, Ari V. ;

Wurtz, Peter ;

Havulinna, Aki S. ;

Aalto, Kristiina ;

Pitkanen, Niina ;

Lehtimaki, Terho ;

Kahonen, Mika ;

Lyytikainen, Leo-Pekka ;

Raitoharju, Emma ;

Seppala, Ilkka ;

Sarin, Antti-Pekka ;

Ripatti, Samuli ;

Palotie, Aarne ;

Perola, Markus ;

Viikari, Jorma S. ;

Jalkanen, Sirpa ;

Maksimow, Mikael ;

Salomaa, Veikko ;

Salmi, Marko ;

Kettunen, Johannes ;

Raitakari, Olli T. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2017, 100 (01) :40-50

[2] Aging and ABO blood type influence von Willebrand factor and factor VIII levels through interrelated mechanisms [J].

Albanez, S. ;

Ogiwara, K. ;

Michels, A. ;

Hopman, W. ;

Grabell, J. ;

James, P. ;

Lillicrap, D. .

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2016, 14 (05) :953-963

[3] Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis [J].

Allen, Richard J. ;

Guillen-Guio, Beatriz ;

Oldham, Justin M. ;

Ma, Shwu-Fan ;

Dressen, Amy ;

Paynton, Megan L. ;

Kraven, Luke M. ;

Obeidat, Ma'en ;

Li, Xuan ;

Ng, Michael ;

Braybrooke, Rebecca ;

Molina-Molina, Maria ;

Hobbs, Brian D. ;

Putman, Rachel K. ;

Sakornsakolpat, Phuwanat ;

Booth, Helen L. ;

Fahy, William A. ;

Hart, Simon P. ;

Hill, Mike R. ;

Hirani, Nik ;

Hubbard, Richard B. ;

McAnulty, Robin J. ;

Millar, Ann B. ;

Navaratnam, Vidyia ;

Oballa, Eunice ;

Parfrey, Helen ;

Saini, Gauri ;

Whyte, Moira K. B. ;

Zhang, Yingze ;

Kaminski, Naftali ;

Adegunsoye, Ayodeji ;

Strek, Mary E. ;

Neighbors, Margaret ;

Sheng, Xuting R. ;

Gudmundsson, Gunnar ;

Gudnason, Vilmundur ;

Hatabu, Hiroto ;

Lederer, David J. ;

Manichaikul, Ani ;

Newell, John D., Jr. ;

O'Connor, George T. ;

Ortega, Victor E. ;

Xu, Hanfei ;

Fingerlin, Tasha E. ;

Bosse, Yohan ;

Hao, Ke ;

Joubert, Philippe ;

Nickle, David C. ;

Sin, Don D. ;

Timens, Wim .

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2020, 201 (05) :564-574

[4] A global reference for human genetic variation [J].

Altshuler, David M. ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Donnelly, Peter ;

Eichler, Evan E. ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Green, Eric D. ;

Hurles, Matthew E. ;

Knoppers, Bartha M. ;

Korbel, Jan O. ;

Lander, Eric S. ;

Lee, Charles ;

Lehrach, Hans ;

Mardis, Elaine R. ;

Marth, Gabor T. ;

McVean, Gil A. ;

Nickerson, Deborah A. ;

Wang, Jun ;

Wilson, Richard K. ;

Boerwinkle, Eric ;

Doddapaneni, Harsha ;

Han, Yi ;

Korchina, Viktoriya ;

Kovar, Christie ;

Lee, Sandra ;

Muzny, Donna ;

Reid, Jeffrey G. ;

Zhu, Yiming ;

Chang, Yuqi ;

Feng, Qiang ;

Fang, Xiaodong ;

Guo, Xiaosen ;

Jian, Min ;

Jiang, Hui ;

Jin, Xin ;

Lan, Tianming ;

Li, Guoqing ;

Li, Jingxiang ;

Li, Yingrui ;

Liu, Shengmao ;

Liu, Xiao ;

Lu, Yao ;

Ma, Xuedi ;

Tang, Meifang ;

Wang, Bo .

NATURE, 2015, 526 (7571) :68-+

[5]

Amraei Razie, 2021, ACS Cent Sci, V7, P1156, DOI [10.1101/2020.06.22.165803, 10.1101/2020.06.22.165803, 10.1021/acscentsci.0c01537]

[6] Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer [J].

Amundadottir, Laufey ;

Kraft, Peter ;

Stolzenberg-Solomon, Rachael Z. ;

Fuchs, Charles S. ;

Petersen, Gloria M. ;

Arslan, Alan A. ;

Bueno-de-Mesquita, H. Bas ;

Gross, Myron ;

Helzlsouer, Kathy ;

Jacobs, Eric J. ;

LaCroix, Andrea ;

Zheng, Wei ;

Albanes, Demetrius ;

Bamlet, William ;

Berg, Christine D. ;

Berrino, Franco ;

Bingham, Sheila ;

Buring, Julie E. ;

Bracci, Paige M. ;

Canzian, Federico ;

Clavel-Chapelon, Francoise ;

Clipp, Sandra ;

Cotterchio, Michelle ;

de Andrade, Mariza ;

Duell, Eric J. ;

Fox, John W., Jr. ;

Gallinger, Steven ;

Gaziano, J. Michael ;

Giovannucci, Edward L. ;

Goggins, Michael ;

Gonzalez, Carlos A. ;

Hallmans, Goran ;

Hankinson, Susan E. ;

Hassan, Manal ;

Holly, Elizabeth A. ;

Hunter, David J. ;

Hutchinson, Amy ;

Jackson, Rebecca ;

Jacobs, Kevin B. ;

Jenab, Mazda ;

Kaaks, Rudolf ;

Klein, Alison P. ;

Kooperberg, Charles ;

Kurtz, Robert C. ;

Li, Donghui ;

Lynch, Shannon M. ;

Mandelson, Margaret ;

McWilliams, Robert R. ;

Mendelsohn, Julie B. ;

Michaud, Dominique S. .

NATURE GENETICS, 2009, 41 (09) :986-U47

[7] The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans [J].

Ardlie, Kristin G. ;

DeLuca, David S. ;

Segre, Ayellet V. ;

Sullivan, Timothy J. ;

Young, Taylor R. ;

Gelfand, Ellen T. ;

Trowbridge, Casandra A. ;

Maller, Julian B. ;

Tukiainen, Taru ;

Lek, Monkol ;

Ward, Lucas D. ;

Kheradpour, Pouya ;

Iriarte, Benjamin ;

Meng, Yan ;

Palmer, Cameron D. ;

Esko, Tonu ;

Winckler, Wendy ;

Hirschhorn, Joel N. ;

Kellis, Manolis ;

MacArthur, Daniel G. ;

Getz, Gad ;

Shabalin, Andrey A. ;

Li, Gen ;

Zhou, Yi-Hui ;

Nobel, Andrew B. ;

Rusyn, Ivan ;

Wright, Fred A. ;

Lappalainen, Tuuli ;

Ferreira, Pedro G. ;

Ongen, Halit ;

Rivas, Manuel A. ;

Battle, Alexis ;

Mostafavi, Sara ;

Monlong, Jean ;

Sammeth, Michael ;

Mele, Marta ;

Reverter, Ferran ;

Goldmann, Jakob M. ;

Koller, Daphne ;

Guigo, Roderic ;

McCarthy, Mark I. ;

Dermitzakis, Emmanouil T. ;

Gamazon, Eric R. ;

Im, Hae Kyung ;

Konkashbaev, Anuar ;

Nicolae, Dan L. ;

Cox, Nancy J. ;

Flutre, Timothee ;

Wen, Xiaoquan ;

Stephens, Matthew .

SCIENCE, 2015, 348 (6235) :648-660

[8] The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease [J].

Astle, William J. ;

Elding, Heather ;

Jiang, Tao ;

Allen, Dave ;

Ruklisa, Dace ;

Mann, Alice L. ;

Mead, Daniel ;

Bouman, Heleen ;

Riveros-Mckay, Fernando ;

Kostadima, Myrto A. ;

Lambourne, John J. ;

Sivapalaratnam, Suthesh ;

Downes, Kate ;

Kundu, Kousik ;

Bomba, Lorenzo ;

Berentsen, Kim ;

Bradley, John R. ;

Daugherty, Louise C. ;

Delaneau, Olivier ;

Freson, Kathleen ;

Garner, Stephen F. ;

Grassi, Luigi ;

Guerrero, Jose ;

Haimel, Matthias ;

Janssen-Megens, Eva M. ;

Kaan, Anita ;

Kamat, Mihir ;

Kim, Bowon ;

Mandoli, Amit ;

Marchini, Jonathan ;

Martens, Joost H. A. ;

Meacham, Stuart ;

Megy, Karyn ;

O'Connell, Jared ;

Petersen, Romina ;

Sharifi, Nilofar ;

Sheard, Simon M. ;

Staley, James R. ;

Tuna, Salih ;

van der Ent, Martijn ;

Walter, Klaudia ;

Wang, Shuang-Yin ;

Wheeler, Eleanor ;

Wilder, Steven P. ;

Iotchkova, Valentina ;

Moore, Carmel ;

Sambrook, Jennifer ;

Stunnenberg, Hendrik G. ;

Di Angelantonio, Emanuele ;

Kaptoge, Stephen .

CELL, 2016, 167 (05) :1415-+

[9] Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania [J].

Band, Gavin ;

Le, Quang Si ;

Clarke, Geraldine M. ;

Kivinen, Katja ;

Hubbart, Christina ;

Jeffreys, Anna E. ;

Rowlands, Kate ;

Leffler, Ellen M. ;

Jallow, Muminatou ;

Conway, David J. ;

Sisay-Joof, Fatoumatta ;

Sirugo, Giorgio ;

d'Alessandro, Umberto ;

Toure, Ousmane B. ;

Thera, Mahamadou A. ;

Konate, Salimata ;

Sissoko, Sibiri ;

Mangano, Valentina D. ;

Bougouma, Edith C. ;

Sirima, Sodiomon B. ;

Amenga-Etego, Lucas N. ;

Ghansah, Anita K. ;

Hodgson, Abraham V. O. ;

Wilson, Michael D. ;

Enimil, Anthony ;

Ansong, Daniel ;

Evans, Jennifer ;

Ademola, Subulade A. ;

Apinjoh, Tobias O. ;

Ndila, Carolyne M. ;

Manjurano, Alphaxard ;

Drakeley, Chris ;

Reyburn, Hugh ;

Nguyen Hoan Phu ;

Nguyen Thi Ngoc Quyen ;

Cao Quang Thai ;

Tran Tinh Hien ;

Teo, Yik Ying ;

Manning, Laurens ;

Laman, Moses ;

Michon, Pascal ;

Karunajeewa, Harin ;

Siba, Peter ;

Allen, Steve ;

Allen, Angela ;

Bahlo, Melanie ;

Davis, Timothy M. E. ;

Simpson, Victoria ;

Shelton, Jennifer ;

Spencer, Chris C. A. .

NATURE COMMUNICATIONS, 2019, 10

[10] A novel locus of resistance to severe malaria in a region of ancient balancing selection [J].

Band, Gavin ;

Rockett, Kirk A. ;

Spencer, Chris C. A. ;

Kwiatkowski, Dominic P. ;

Band, Gavin ;

Le, Quang Si ;

Clarke, Geraldine M. ;

Kivinen, Katja ;

Leffler, Ellen M. ;

Rockett, Kirk A. ;

Kwiatkowski, Dominic P. ;

Spencer, Chris C. A. ;

Rockett, Kirk A. ;

Spencer, Chris C. A. ;

Cornelius, Victoria ;

Conway, David J. ;

Williams, Thomas N. ;

Taylor, Terrie ;

Kwiatkowski, Dominic P. ;

Conway, David J. ;

Bojang, Kalifa A. ;

Doumbo, Ogobara ;

Thera, Mahamadou A. ;

Modiano, David ;

Sirima, Sodiomon B. ;

Wilson, Michael D. ;

Koram, Kwadwo A. ;

Agbenyega, Tsiri ;

Achidi, Eric ;

Williams, Thomas N. ;

Marsh, Kevin ;

Reyburn, Hugh ;

Drakeley, Chris ;

Riley, Eleanor ;

Taylor, Terrie ;

Molyneux, Malcolm ;

Jallow, Muminatou ;

Bojang, Kalifa A. ;

Conway, David J. ;

Pinder, Margaret ;

Doumbo, Ogobara ;

Thera, Mahamadou A. ;

Toure, Ousmane B. ;

Konate, Salimata ;

Sissoko, Sibiri ;

Bougouma, Edith C. ;

Mangano, Valentina D. ;

Modiano, David ;

Sirima, Sodiomon B. ;

Amenga-Etego, Lucas N. .

NATURE, 2015, 526 (7572) :253-+

← 1 2 3 4 5 6 7 8 9 10 →

共 118 条

[1] Genome-wide Association Study Identifies 27 Loci Influencing Concentrations of Circulating Cytokines and Growth Factors [J].

Ahola-Olli, Ari V. ;

Wurtz, Peter ;

Havulinna, Aki S. ;

Aalto, Kristiina ;

Pitkanen, Niina ;

Lehtimaki, Terho ;

Kahonen, Mika ;

Lyytikainen, Leo-Pekka ;

Raitoharju, Emma ;

Seppala, Ilkka ;

Sarin, Antti-Pekka ;

Ripatti, Samuli ;

Palotie, Aarne ;

Perola, Markus ;

Viikari, Jorma S. ;

Jalkanen, Sirpa ;

Maksimow, Mikael ;

Salomaa, Veikko ;

Salmi, Marko ;

Kettunen, Johannes ;

Raitakari, Olli T. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2017, 100 (01) :40-50

[2] Aging and ABO blood type influence von Willebrand factor and factor VIII levels through interrelated mechanisms [J].

Albanez, S. ;

Ogiwara, K. ;

Michels, A. ;

Hopman, W. ;

Grabell, J. ;

James, P. ;

Lillicrap, D. .

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2016, 14 (05) :953-963

[3] Genome-Wide Association Study of Susceptibility to Idiopathic Pulmonary Fibrosis [J].

Allen, Richard J. ;

Guillen-Guio, Beatriz ;

Oldham, Justin M. ;

Ma, Shwu-Fan ;

Dressen, Amy ;

Paynton, Megan L. ;

Kraven, Luke M. ;

Obeidat, Ma'en ;

Li, Xuan ;

Ng, Michael ;

Braybrooke, Rebecca ;

Molina-Molina, Maria ;

Hobbs, Brian D. ;

Putman, Rachel K. ;

Sakornsakolpat, Phuwanat ;

Booth, Helen L. ;

Fahy, William A. ;

Hart, Simon P. ;

Hill, Mike R. ;

Hirani, Nik ;

Hubbard, Richard B. ;

McAnulty, Robin J. ;

Millar, Ann B. ;

Navaratnam, Vidyia ;

Oballa, Eunice ;

Parfrey, Helen ;

Saini, Gauri ;

Whyte, Moira K. B. ;

Zhang, Yingze ;

Kaminski, Naftali ;

Adegunsoye, Ayodeji ;

Strek, Mary E. ;

Neighbors, Margaret ;

Sheng, Xuting R. ;

Gudmundsson, Gunnar ;

Gudnason, Vilmundur ;

Hatabu, Hiroto ;

Lederer, David J. ;

Manichaikul, Ani ;

Newell, John D., Jr. ;

O'Connor, George T. ;

Ortega, Victor E. ;

Xu, Hanfei ;

Fingerlin, Tasha E. ;

Bosse, Yohan ;

Hao, Ke ;

Joubert, Philippe ;

Nickle, David C. ;

Sin, Don D. ;

Timens, Wim .

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2020, 201 (05) :564-574

[4] A global reference for human genetic variation [J].

Altshuler, David M. ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Donnelly, Peter ;

Eichler, Evan E. ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Green, Eric D. ;

Hurles, Matthew E. ;

Knoppers, Bartha M. ;

Korbel, Jan O. ;

Lander, Eric S. ;

Lee, Charles ;

Lehrach, Hans ;

Mardis, Elaine R. ;

Marth, Gabor T. ;

McVean, Gil A. ;

Nickerson, Deborah A. ;

Wang, Jun ;

Wilson, Richard K. ;

Boerwinkle, Eric ;

Doddapaneni, Harsha ;

Han, Yi ;

Korchina, Viktoriya ;

Kovar, Christie ;

Lee, Sandra ;

Muzny, Donna ;

Reid, Jeffrey G. ;

Zhu, Yiming ;

Chang, Yuqi ;

Feng, Qiang ;

Fang, Xiaodong ;

Guo, Xiaosen ;

Jian, Min ;

Jiang, Hui ;

Jin, Xin ;

Lan, Tianming ;

Li, Guoqing ;

Li, Jingxiang ;

Li, Yingrui ;

Liu, Shengmao ;

Liu, Xiao ;

Lu, Yao ;

Ma, Xuedi ;

Tang, Meifang ;

Wang, Bo .

NATURE, 2015, 526 (7571) :68-+

[5]

Amraei Razie, 2021, ACS Cent Sci, V7, P1156, DOI [10.1101/2020.06.22.165803, 10.1101/2020.06.22.165803, 10.1021/acscentsci.0c01537]

[6] Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer [J].

Amundadottir, Laufey ;

Kraft, Peter ;

Stolzenberg-Solomon, Rachael Z. ;

Fuchs, Charles S. ;

Petersen, Gloria M. ;

Arslan, Alan A. ;

Bueno-de-Mesquita, H. Bas ;

Gross, Myron ;

Helzlsouer, Kathy ;

Jacobs, Eric J. ;

LaCroix, Andrea ;

Zheng, Wei ;

Albanes, Demetrius ;

Bamlet, William ;

Berg, Christine D. ;

Berrino, Franco ;

Bingham, Sheila ;

Buring, Julie E. ;

Bracci, Paige M. ;

Canzian, Federico ;

Clavel-Chapelon, Francoise ;

Clipp, Sandra ;

Cotterchio, Michelle ;

de Andrade, Mariza ;

Duell, Eric J. ;

Fox, John W., Jr. ;

Gallinger, Steven ;

Gaziano, J. Michael ;

Giovannucci, Edward L. ;

Goggins, Michael ;

Gonzalez, Carlos A. ;

Hallmans, Goran ;

Hankinson, Susan E. ;

Hassan, Manal ;

Holly, Elizabeth A. ;

Hunter, David J. ;

Hutchinson, Amy ;

Jackson, Rebecca ;

Jacobs, Kevin B. ;

Jenab, Mazda ;

Kaaks, Rudolf ;

Klein, Alison P. ;

Kooperberg, Charles ;

Kurtz, Robert C. ;

Li, Donghui ;

Lynch, Shannon M. ;

Mandelson, Margaret ;

McWilliams, Robert R. ;

Mendelsohn, Julie B. ;

Michaud, Dominique S. .

NATURE GENETICS, 2009, 41 (09) :986-U47

[7] The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans [J].

Ardlie, Kristin G. ;

DeLuca, David S. ;

Segre, Ayellet V. ;

Sullivan, Timothy J. ;

Young, Taylor R. ;

Gelfand, Ellen T. ;

Trowbridge, Casandra A. ;

Maller, Julian B. ;

Tukiainen, Taru ;

Lek, Monkol ;

Ward, Lucas D. ;

Kheradpour, Pouya ;

Iriarte, Benjamin ;

Meng, Yan ;

Palmer, Cameron D. ;

Esko, Tonu ;

Winckler, Wendy ;

Hirschhorn, Joel N. ;

Kellis, Manolis ;

MacArthur, Daniel G. ;

Getz, Gad ;

Shabalin, Andrey A. ;

Li, Gen ;

Zhou, Yi-Hui ;

Nobel, Andrew B. ;

Rusyn, Ivan ;

Wright, Fred A. ;

Lappalainen, Tuuli ;

Ferreira, Pedro G. ;

Ongen, Halit ;

Rivas, Manuel A. ;

Battle, Alexis ;

Mostafavi, Sara ;

Monlong, Jean ;

Sammeth, Michael ;

Mele, Marta ;

Reverter, Ferran ;

Goldmann, Jakob M. ;

Koller, Daphne ;

Guigo, Roderic ;

McCarthy, Mark I. ;

Dermitzakis, Emmanouil T. ;

Gamazon, Eric R. ;

Im, Hae Kyung ;

Konkashbaev, Anuar ;

Nicolae, Dan L. ;

Cox, Nancy J. ;

Flutre, Timothee ;

Wen, Xiaoquan ;

Stephens, Matthew .

SCIENCE, 2015, 348 (6235) :648-660

[8] The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease [J].

Astle, William J. ;

Elding, Heather ;

Jiang, Tao ;

Allen, Dave ;

Ruklisa, Dace ;

Mann, Alice L. ;

Mead, Daniel ;

Bouman, Heleen ;

Riveros-Mckay, Fernando ;

Kostadima, Myrto A. ;

Lambourne, John J. ;

Sivapalaratnam, Suthesh ;

Downes, Kate ;

Kundu, Kousik ;

Bomba, Lorenzo ;

Berentsen, Kim ;

Bradley, John R. ;

Daugherty, Louise C. ;

Delaneau, Olivier ;

Freson, Kathleen ;

Garner, Stephen F. ;

Grassi, Luigi ;

Guerrero, Jose ;

Haimel, Matthias ;

Janssen-Megens, Eva M. ;

Kaan, Anita ;

Kamat, Mihir ;

Kim, Bowon ;

Mandoli, Amit ;

Marchini, Jonathan ;

Martens, Joost H. A. ;

Meacham, Stuart ;

Megy, Karyn ;

O'Connell, Jared ;

Petersen, Romina ;

Sharifi, Nilofar ;

Sheard, Simon M. ;

Staley, James R. ;

Tuna, Salih ;

van der Ent, Martijn ;

Walter, Klaudia ;

Wang, Shuang-Yin ;

Wheeler, Eleanor ;

Wilder, Steven P. ;

Iotchkova, Valentina ;

Moore, Carmel ;

Sambrook, Jennifer ;

Stunnenberg, Hendrik G. ;

Di Angelantonio, Emanuele ;

Kaptoge, Stephen .

CELL, 2016, 167 (05) :1415-+

[9] Insights into malaria susceptibility using genome-wide data on 17,000 individuals from Africa, Asia and Oceania [J].

Band, Gavin ;

Le, Quang Si ;

Clarke, Geraldine M. ;

Kivinen, Katja ;

Hubbart, Christina ;

Jeffreys, Anna E. ;

Rowlands, Kate ;

Leffler, Ellen M. ;

Jallow, Muminatou ;

Conway, David J. ;

Sisay-Joof, Fatoumatta ;

Sirugo, Giorgio ;

d'Alessandro, Umberto ;

Toure, Ousmane B. ;

Thera, Mahamadou A. ;

Konate, Salimata ;

Sissoko, Sibiri ;

Mangano, Valentina D. ;

Bougouma, Edith C. ;

Sirima, Sodiomon B. ;

Amenga-Etego, Lucas N. ;

Ghansah, Anita K. ;

Hodgson, Abraham V. O. ;

Wilson, Michael D. ;

Enimil, Anthony ;

Ansong, Daniel ;

Evans, Jennifer ;

Ademola, Subulade A. ;

Apinjoh, Tobias O. ;

Ndila, Carolyne M. ;

Manjurano, Alphaxard ;

Drakeley, Chris ;

Reyburn, Hugh ;

Nguyen Hoan Phu ;

Nguyen Thi Ngoc Quyen ;

Cao Quang Thai ;

Tran Tinh Hien ;

Teo, Yik Ying ;

Manning, Laurens ;

Laman, Moses ;

Michon, Pascal ;

Karunajeewa, Harin ;

Siba, Peter ;

Allen, Steve ;

Allen, Angela ;

Bahlo, Melanie ;

Davis, Timothy M. E. ;

Simpson, Victoria ;

Shelton, Jennifer ;

Spencer, Chris C. A. .

NATURE COMMUNICATIONS, 2019, 10

[10] A novel locus of resistance to severe malaria in a region of ancient balancing selection [J].

Band, Gavin ;

Rockett, Kirk A. ;

Spencer, Chris C. A. ;

Kwiatkowski, Dominic P. ;

Band, Gavin ;

Le, Quang Si ;

Clarke, Geraldine M. ;

Kivinen, Katja ;

Leffler, Ellen M. ;

Rockett, Kirk A. ;

Kwiatkowski, Dominic P. ;

Spencer, Chris C. A. ;

Rockett, Kirk A. ;

Spencer, Chris C. A. ;

Cornelius, Victoria ;

Conway, David J. ;

Williams, Thomas N. ;

Taylor, Terrie ;

Kwiatkowski, Dominic P. ;

Conway, David J. ;

Bojang, Kalifa A. ;

Doumbo, Ogobara ;

Thera, Mahamadou A. ;

Modiano, David ;

Sirima, Sodiomon B. ;

Wilson, Michael D. ;

Koram, Kwadwo A. ;

Agbenyega, Tsiri ;

Achidi, Eric ;

Williams, Thomas N. ;

Marsh, Kevin ;

Reyburn, Hugh ;

Drakeley, Chris ;

Riley, Eleanor ;

Taylor, Terrie ;

Molyneux, Malcolm ;

Jallow, Muminatou ;

Bojang, Kalifa A. ;

Conway, David J. ;

Pinder, Margaret ;

Doumbo, Ogobara ;

Thera, Mahamadou A. ;

Toure, Ousmane B. ;

Konate, Salimata ;

Sissoko, Sibiri ;

Bougouma, Edith C. ;

Mangano, Valentina D. ;

Modiano, David ;

Sirima, Sodiomon B. ;

Amenga-Etego, Lucas N. .

NATURE, 2015, 526 (7572) :253-+

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